A computer based system of image analysis has been applied to objective simultaneous and hierarchical classification of various classes urothelial cells in the sediment of voided human urine. An automated system of cell triage and classification has been developed and has led to the construction of cytologic profiles of diagnostic value in a test group of patients with bladder cancer. These initial results were achieved with the help of newly developed methods of laboratory processing of urinary sediment and through effective programming of a small laboratory computer. Prior work has also led to an initial accumulation of morphometric data on urothelial cells that may provide additional guidelines to the diagnostic and prognostic classification of cell images. The purpose of this grant application is to determine the clinical value of the experimental system as a tool in the detection, diagnosis and prognosis of urothelial cancer. To this purpose, we propose to study a statistically valid sample of patients with this disease and suitable controls by methods outlined in this application. It is of particular interest to confirm the significance and clinical value of cytologic profiles of patients and controls. The hierarchical classification method will be used as a tool in the analysis of complex cell populations by computer. The diagnostic and prognostic value of morphometric analysis of cell images strined with either Papanicolaou or Feulgen methods will be tested as it may contribute to the objective identification of diagnostically important subgroups of urothelial cells characterizing patients at high risk of invasive carcinoma. The study explores the practical and diagnostic value of computer technology applied to a notoriously difficult diagnostic target, the analysis of cells in the sediment of voided urine, the principal non-invasive method of diagnosis of urothelial cancer. In the broader sense, the study tests the powers of significance of objective analysis of cell images by computer that may find application in many other aspects of cancer cell research. The study may also lead to the construction of an automated clinical laboratory instrument similar in concept to devices for differential blood counts.